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Item Recent Advances in Understanding Bisphosphonate Effects on Bone Mechanical Properties(Springer, 2018-04) Allen, Matthew R.; Anatomy and Cell Biology, School of MedicinePurpose of the Review Bisphosphonates have well-established effects on suppressing bone resorption and slowing bone loss, yet the effects on bone mechanical properties are less clear. We review recent data from pre-clinical and clinical experiments that assessed mechanical properties of bisphosphonate-treated specimens. Recent Findings Pre-clinical work has utilized new techniques to show reduced fatigue life and transfer of stress from the mineral to collagen. Several notable studies have examined mechanical properties of tissue from patients treated with bisphosphonates with mixed results. Pre-clinical data suggest effects on mechanics may be independent of remodeling suppression. Summary The direct effect of bisphosphonates on bone mechanics remains unclear but recent work has set a solid foundation for the coming years.Item The Resistance of Cortical Bone Tissue to Failure under Cyclic Loading is Reduced with Alendronate(Elsevier B.V., 2014-07) Bajaj, Devendra; Geissler, Joseph R.; Allen, Matthew R.; Burr, David B.; Fritton, J. Christopher; Department of Anatomy & Cell Biology, IU School of MedicineBisphosphonates are the most prescribed preventative treatment for osteoporosis. However, their long-term use has recently been associated with atypical fractures of cortical bone in patients who present with low-energy induced breaks of unclear pathophysiology. The effects of bisphosphonates on the mechanical properties of cortical bone have been exclusively studied under simple, monotonic, quasi-static loading. This study examined the cyclic fatigue properties of bisphosphonate-treated cortical bone at a level in which tissue damage initiates and is accumulated prior to frank fracture in low-energy situations. Physiologically relevant, dynamic, 4-point bending applied to beams (1.5 mm × 0.5 mm × 10 mm) machined from dog rib (n=12/group) demonstrated mechanical failure and micro-architectural features that were dependent on drug dose (3 groups: 0, 0.2, 1.0 mg/kg/day; Alendronate [ALN] for 3 years) with cortical bone tissue elastic modulus (initial cycles of loading) reduced by 21% (p<0.001) and fatigue life (number of cycles to failure) reduced in a stress-life approach by greater than 3-fold with ALN1.0 (p<0.05). While not affecting the number of osteons, ALN treatment reduced other features associated with bone remodeling, such as the size of osteons (−14%, ALN1.0: 10.5±1.8, VEH: 12.2±1.6, ×103 µm2; p<0.01) and the density of osteocyte lacunae (−20%; ALN1.0: 11.4±3.3, VEH: 14.3±3.6, ×102 #/mm2; p<0.05). Furthermore, the osteocyte lacunar density was directly proportional to initial elastic modulus when the groups were pooled (R=0.54, p<0.01). These findings suggest that the structural components normally contributing to healthy cortical bone tissue are altered by high-dose ALN treatment and contribute to reduced mechanical properties under cyclic loading conditions.